Vitamin D analogs and methods of preparing these compounds

Abstract

The invention relates to vitamin D analogs of general formula (I) wherein: R1 is a hydrogen atom or a substituent selected from the group consisting of hydroxy, CH2OH, CH2CH2OH, CH2CH2CH2OH, OCH3, OCH2OH, OCH2CH2OH and OCH2CH2CH2OH; R2 is a hydrogen atom or a substituent selected from the group consisting of OCH3, OCH2OH, CHm(CH2OH)n(CH2CH2OH)p, (CH2)qOH and O(CH2)rOH; wherein: m is 0 or 1, p, q and n are 0-3, r is 1-3 and m+n+p=3; with the proviso that R1 and/or R2 contain at least one OH group; R3 is a straight or branched, saturated or unsaturated aliphatic hydrocarbon of 6-13 C atoms which may be substituted with one or more substituents from the group hydroxy or fluoro. The invention further relates to methods of preparing these compounds, a pharmaceutical composition containing these compounds and to their use in pharmacotherapy and cosmetics.

What is claimed is:  
     
       1. A vitamin D compound of formula (I):                    
       wherein: 
       R 1  is a hydrogen atom or a substituent selected from the group consisting of OH, CH 2 OH, CH 2 CH 2 OH, CH 2 CH 2 CH 2 OH, OCH 3 , OCH 2 OH, OCH 2 CH 2 OH and OCH 2 CH 2 CH 2 OH;  
       R 2  is a hydrogen atom or a substituent selected from the group consisting of OCH 3 , OCH 2 OH, CH m (CH 2 OH) n (CH 2 CH 2 OH) p , (CH 2 ) q OH and O(CH 2 ) r OH;  
       wherein: 
       m is 0 or 1; p, q, and n are independently 0, 1, 2 or 3; r is 1, 2 or 3;  
       and m+n+p=3;  
       with the proviso that at least one of R 1  and R 2  contains at least one OH group and; 
       with the proviso that both R 1  substituents are the same; 
       R 3  is a straight or branched, saturated or unsaturated aliphatic hydrocarbon having from 6 to 13 carbon atoms which may be substituted with one or more substituents selected from the group consisting of hydroxy and fluoro. 
     
     
       2. The compound of formula (I) as claimed in claim  1 , wherein R 3  is —(CH 2 ) 3 —C(CH 3 ) 2 OH. 
     
     
       3. The compound of formula (I) as claimed in claim  2 , wherein: 
       (a) R 1  is a hydrogen atom and R 2  represents CH 2 CH 2 OH, CH 2 CH 2 CH 2 OH, CH(CH 2 CH 2 OH) 2 , C(CH 2 CH 2 OH) 3  or C(CH 2 CH 2 OH) 2 CH 2 OH; or  
       (b) R 1  is OH, CH 2 OH or (CH 2 ) 2 OH and R 2  represents hydrogen, OH, OCH 3 , or O(CH 2 ) r OH, wherein r has the value 1, 2 or 3.  
     
     
       4. The compound of formula (I) as claimed in claim  1 , wherein R 1  is hydroxy, CH 2 OH or CH 2 CH 2 OH, and R 2  represents hydrogen, CH 2 OH or CH 2 CH 2 OH. 
     
     
       5. A method for preparing the vitamin D compound claimed in claim  1 , which method comprises 
       reacting, under the influence of an alkyl lithium compound, a zinc halogenide, and a transmetallation catalyst, a compound of formula (IV):                    
       wherein: 
       R 3 ′ is a straight or branched, saturated or unsaturated aliphatic hydrocarbon having from 6 to 13 carbon atoms which may be substituted with one or more substituents selected from the group consisting of protected hydroxy and fluoro; and  
       R 4  is a protected hydroxy group;  
       with a compound of formula (IIIa):                    
       wherein: 
       X′ is halogen; and  
       R 1 ′ and R 2 ′ are the hydroxy protected forms of groups R 1  and R 2  defined in claim  1 ; and  
       subsequently deprotecting the hydroxy groups of R 1 ′ and R 2 ′. 
     
     
       6. The method of claim  5 , wherein X′ is bromine. 
     
     
       7. The method of claim  5 , wherein the zinc halogenide is zinc chloride. 
     
     
       8. A pharmaceutical composition comprising: 
       a pharmaceutically effective amount of at least one compound of formula (I) defined according to claim  1 , and  
       at least one pharmaceutically acceptable carrier, at least one pharmaceutically acceptable auxiliary substance, or a combination thereof.  
     
     
       9. A method for preparing the pharmaceutical composition claimed in claim  8 , wherein the method comprises combining said pharmaceutically effective amount of at least one compound of formula (I) with said at least one pharmaceutically acceptable carrier, said at least one 
       pharmaceutically acceptable auxiliary substance, or a combination thereof.